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There is no agreement on the standard chemotherapeutic regimen for biliary tract cancer(BTC), although multi-drug regimens such as gemcitabine and/or S-1 have been tested in clinical trials. This study retrospectively reviewed data from patients with BTC who were seen at hospitals in the Kitakyushu and Fukuoka areas between 2005 and 2006, and examined the effect of systemic chemotherapy regimen on survival benefits in patients with unresectable BTC. Chemotherapy may benefit patients with BTC any age group, regardless of the primary site.

The patient was a 70-year-old man with metastatic pancreatic cancer. After he received combination chemotherapy with gemcitabine and oral S-1 on day 1, he experienced severe general fatigue, anorexia and nausea. Then we changed the dose of gemcitabine from 1,000 mg/m(2) 2 to 500 mg/m(2) according to the criteria for an individual maximum repeatable dose (iMRD) determination method on day 8. His general condition recovered, and treatment schedule of gemcitabine with S-1 was continued sequentially at an outpatient clinic. His tumor marker levels, and the sizes of primary pancreatic tumor and liver metastatic lesions remarkably decreased. Partial response has been obtained for 7 months.

The aim of this phase I/II study was to evaluate the tolerability and efficacy of combination chemotherapy with gemcitabine (GEM) and UFT for advanced pancreatic cancer. In phase I study UFT was given orally every day for 14 days and GEM was infused on day 1 and 8 at three dose levels (800, 900, 1,000 mg/m(2)/week) every 21 days. GEM 1,000 mg/m(2) and UFT 400 mg/m(2) did not reach the maximum tolerated dose. We decided that the recommended dose (RD) was GEM 1,000 mg/m(2)and UFT 400 mg/m(2). In phase II study 27 patients were enrolled and received GEM and UFT at RD. The tumor response rate was 17.6%, and the median survival was 221 days, which was very similar to that of GEM monotherapy. Due to adverse events, especially liver dysfunction, protocol therapy was discontinued in 12 patients. This study could not revealed the superiority of the GEM monotherapy.

In two patients with advanced pancreatic cancer with cervical lymph node or liver metastasis and no indication of pancreatic resection and radiotherapy, oral treatment with S-1 (an anti-cancer agent of fluoropyrimidine derivative) exerted high anti-tumor activity on the metastatic lesions. Both cases responded well to this therapy in the late phase II study of S-1 in patients with advanced pancreatic cancer designed to evaluate efficacy and safety. In Case 1 (with cervical lymph node metastasis), the anti-tumor efficacy of this therapy was evaluated as a partial response (PR) after the first four courses of treatment. In Case 2 (with liver metastasis), the efficacy was evaluated as PR for overall response. Thus, the therapy indicated excellent efficacy in both cases. No grade 3 or severe adverse event was noted in either of the two cases. In Case 1, grade 2 anemia, stomatitis, vomiting and fatigue, and some other mild events were noted. When used as a systemic chemotherapy for metastatic pancreatic cancer, oral treatment of S-1 is highly effective, tolerable and convenient in an outpatient clinic. This drug is a promising way to improve and preserve the QOL essential to long-term home care.

Eighteen patients with metastatic or post-surgery recurrent pancreatic cancer were given weekly gemcitabine therapy. Almost all of these patients were aged or had other complications. We determined the individualized maximum repeatable dose (iMRD)as follows. We started at 500 mg/m(2) gemcitabine and repeated the treatment with an increase or a decrease of 100mg/m(2) each week, if the hematological toxicity was 0 or more than grade 1. If toxicity was grade 1, the same dose was given. And the third-week dose was an iMRD. Dose intensity was 286 mg/m(2)/week. The median survival time was 262 days. Of these 18 patients, 2 (11.1%), 11(61.1%) and 5 (27.8%) patients showed partial response, stable disease, and progressive disease, respectively. The therapeutic effects of iMRD equaled those of standard administration of gemcitabine.

We describe the present and future directions of home therapy in pancreatic cancer patients according to the chemotherapy and best supportive care. Chemotherapy in an outpatient clinic is widely supported by the use of gemcitabine, and useful because of mild adverse effect, good clinical benefit response and survival benefit. Since there is no secondary chemotherapy agent after gemcitabine treatment failure, best supportive care is essential. Control of blood glucose level, ascites and pain are also important. Now pain control and home therapy are easy to perform because of the development of various useful opioid agents.

A 17-year-old man was admitted to hospital because of epigastric pain. Various imaging studies showed a solid tumor (4cm in diameter) in the tail of the pancreas, multiple hypovascular tumors in liver. Serum levels of DUPAN2, SPAN1 and NSE were elevated slightly. Biopsy of hepatic tumor demonstrated that tumor cells had eosinophilic cytoplasm generally and unevenly distributed polymorphic nucleus. These data suggested that this tumor is poorly differentiated pancreatic carcinoma originated from the epithelium. Therefore, we administered 5-fluorouracil and cisplatin, combined with gemcitabine. The clinical status improved temporarily by the treatment, however, worsened rapidly. He died 81days after the treatment. Final diagnosis of autopsy was pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma in the young patients is rare, and we reported this case in addition to consideration on literature.

Prognosis of pancreatic cancer is one of the worst among various cancers, however, incidence of bone metastasis has been increased even in pancreatic cancer in recent years. Therefore, we examined clinical features of pancreatic cancer presenting bone metastases who were treated in our cancer center, and propose how to manage these patients. We experienced 13 patients (7.3%) with pancreatic cancer with bone metastases during 2000-2003. Among these patients, pancreatic cancer was located at pancreatic body to tail in 10 cases, while it was located at pancreatic head in 3 cases. Liver metastasis was noted in 7 of 13 cases with bone metastases. Radiographical imagings of bone lesions revealed osteolytic bone destruction, and serum levels of bone resorption marker, 1CTP, were elevated in these patients. Stimulation of osteoclastic bone resorption is a critical step for bone metastasis, thus, serum levels of cytokines (PTHrP, IL-6, VEGF), which exert a promotive effect on bone resorption, were measured. Serum levels of IL-6 and VEGF were elevated in most of these patients, while elevation of serum PTHrP levels was found in 3 of 13 patients with bone metastases. Survival periods of pancreatic cancer patients with bone metastases was not long, however, treatment for bone metastases is important in terms of quality of life (QOL). An earlier diagnosis is essential to prevent deterioration in the QOL of pancreatic cancer patients presenting bone metastases. Periodical measurement of serum 1CTP in addition to bone scintigraphy is helpful for the earlier diagnosis for bone metastases.

Forty-nine patients with unresectable pancreatic cancer (stage IV disease) received gemcitabine in a multi-center trial in the Fukuoka pancreatic cancer chemotherapy group, Japan. No complete remissions, 5 partial remissions (10%) and 25 no changes (51%) were obtained. Gemcitabine could maintain QOL. Main toxicities were hematologic, especially neutropenia. Neutropenia tended to appear in early administration. Non-hematologic toxicities were anorexia, nausea/vomiting, and skin rash. The mean overall survival period was 7.5 months. Carcinomatous ascites and/or pleural effusion resulted in a poor prognosis (average survival 3.1 months). Gemcitabine could be given without severe toxicities in outpatient clinics. These results suggested that gemcitabine is currently a first-line therapeutic agent for advanced pancreatic cancer.

A 62-year-old man with carcinomatous ascites more than 5 years after early gastric cancer operation was admitted to our hospital because of suspected pancreatic cancer, and was diagnosed with a relapse of the gastric cancer. TS-1 was administered at a dose of 120 mg/day. At the end of 1 course a partial response of a decrease of tumor markers and ascites and improvement of QOL was achieved, and the patient was followed in the outpatient clinic. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of gastric cancer relapse with carcinomatous ascites.

A patient with advanced gastric cancer complicated with liver and lymph node metastases was successfully treated with a novel oral anticancer drug, TS-1, TS-1 was administered at a dose of 100 mg/day. One course consisted of consecutive administration of TS-1 for 28 days and withdrawal for 14 days. At the end of 3 courses a partial response of the liver metastases was achieved. Although the patient has had complications with ascites collection due to hypoalbuminemia, he has been well without regrowth of any metastases for over 8 months.